Insensitivity of peptidoglycan biosynthetic reactions to beta-lactam antibiotics in a clinical isolate of Pseudomonas aeruginosa.
The enzymatic reactions (transpeptidases/ that catalyze the attachment of newly synthesized peptidoglycan to the preexisting cell wall sacculus of both Escherichia coli and Pseudomonas aeruginosa have been shown to be very sensitive to most beta-lactam antibiotics. Biosynthetic studies carried out with a clinical isolate of P. aeruginosa resistant to carbenicillin and cefsulodin showed that the in vitro reactions were also insensitive to most beta-lactam antibiotics (up to 50 micrograms/ml) and only cefotaxime or its tetrazolyl analog, compound LY 97962, had an inhibitory effect at 0.01 microgram/ml. The pattern of beta-lactam binding proteins obtained upon exposure of intact or presonicated cells to radioactively labeled compound LY 97962 or penicillin G indicates that: (i) intact cells of the clinical isolate are 10 to 50 times less permeable to the antibiotics than is the wild-type strain X-48; (ii) beta-lactam binding proteins Ia, Ib, and III of the clinical isolate showed poor affinity for penicillin G and cefsulodin, but were similar to the wild type in their affinity for cefotaxime and compound LY 979062. The two strains also differed in several of their outer membrane components. These results suggest that the insusceptibility of this clinical isolate is due to a combination of outer membrane impermeability and intrinsic insensitivity to most of the beta-lactams on the part of the enzymes which catalyze expansion and growth of peptidoglycan.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism; D004352:Drug Resistance, Microbial; D006801:Humans; D010457:Peptidoglycan / Q000096:biosynthesis*; D011485:Protein Binding; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D047090:beta-Lactams; D001618:beta-Lactamases